20-18507755-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000336714.8(SEC23B):c.-250C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 152,388 control chromosomes in the GnomAD database, including 53,630 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (53599 hom., cov: 35)
  • Exomes 𝑓: 0.91 (31 hom.)
• Consequence: SEC23B ENST00000336714.8 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0340

Genes affected

SEC23B (HGNC:10702): (SEC23 homolog B, COPII coat complex component) The protein encoded by this gene is a member of the SEC23 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein has similarity to yeast Sec23p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. The function of this gene product has been implicated in cargo selection and concentration. Multiple alternatively spliced transcript variants have been identified in this gene. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 20-18507755-C-G is Benign according to our data. Variant chr20-18507755-C-G is described in ClinVar as [Benign]. Clinvar id is 337781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC23B	NM_032986.5	c.-15+86C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC23B	ENST00000336714.8	c.-250C>G		5_prime_UTR_variant	1/20	1		P1
SEC23B	ENST00000262544.6	c.-290C>G		5_prime_UTR_variant	1/20	5		P1
SEC23B	ENST00000450074.6	c.-15+86C>G		intron_variant		5
SEC23B	ENST00000646240.1	c.-222+86C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126365 AN: 152194 Hom.: 53583 Cov.: 35

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.847

GnomAD4 exome AF: 0.908 AC: 69 AN: 76 Hom.: 31 Cov.: 0 AF XY: 0.929 AC XY: 52 AN XY: 56

Gnomad4 AMR exome AF: 1.00

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.929

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.830 AC: 126431 AN: 152312 Hom.: 53599 Cov.: 35 AF XY: 0.829 AC XY: 61713 AN XY: 74482

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.880

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.853

Gnomad4 FIN AF: 0.901

Gnomad4 NFE AF: 0.927

Gnomad4 OTH AF: 0.842

Alfa AF: 0.866 Hom.: 2969

Bravo AF: 0.813

Asia WGS AF: 0.747 AC: 2597 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital dyserythropoietic anemia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	3.3
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4813333; hg19: chr20-18488399;